CORE B: CLINICAL - ABSTRACT. In alignment with the UW ADRC's vision of precision medicine for Alzheimer's disease, the Clinical Core is shifting its focus to concentrate on better defining cognitively normal aging and the transition from normal to pathological aging to prodromal AD and the earliest stages of dementia - - in particular, AD dementia. Participants in these groups will be followed, as specified in the RFA, per NACC UDS requirements. We will continue to focus on our Core's traditional strengths of high rates of participation in CSF/plasma/serum collection, autopsy consent, and clinical diagnostic accuracy confirmed on neuropathology, and will conduct innovative work to detect earliest cognitive changes in presymptomatic AD and to make research findings more representative of the general population of older adults. Specific Aim 1: To characterize clinically and follow longitudinally persons with normal aging, and presymptomatic, prodromal, and early stage AD. Participants in the Clinical Core will be selected for participation in ADRC Project 3; ADRC-affiliated clinical research studies, including treatment trials; and likelihood of obtaining CSF, plasma, and serum, neuroimaging, and autopsy. New emphasis will be made to enroll members of the community-based Adult Changes in Thought to broaden generalizability of findings. Developmental work will address detection of earliest cognitive changes associated with presymptomatic AD. Specific Aim 2: To characterize clinically and follow longitudinally participants from two underserved minority communities -- African Americans and American Indians -- with normal aging, and presymptomatic, prodromal, and early stage AD. In collaboration with the Outreach, Recruitment, and Education (ORE) Core, Clinical Core will continue recruiting, enrolling, and following longitudinally African Americans and will also conduct targeted enrollment of urban-dwelling American Indians/Native Alaskans to improve participation by minorities in the full range of human research in normal aging and AD: clinical research studies, treatment trials, genetic and biomarker studies, and autopsy. Specific Aim 3: To provide well-characterized participants for clinical and basic research across the continuum from normal aging through presymptomatic, prodromal, and AD dementia. Participants will be provided for ADRC Project 3, other clinical research at UW and at other institutions, multicenter clinical treatment trials, and multi-ADC collaborative studies such as the AD Genetics Consortium. Specific Aim 4: To obtain and maintain a bank of cerebrospinal fluid (CSF), plasma, and serum samples from well-characterized participants with normal and pathological aging, prodromal and diagnosed AD, and non-AD neurodegenerative dementias. Samples will be provided to UW ADRC and other AD investigators locally and nationally for development of AD biomarkers. The Clinical Core will provide assistance to collaborative studies of CSF biomarkers with respect to methods for obtaining and banking CSF.